Body lumen junction localization

ABSTRACT

Devices, systems, and methods for the localization of body lumen junctions and other intraluminal structure are disclosed. Various embodiments permit clinicians to identify the locations of intraluminal structures and medical devices during non-surgical medical techniques, such as cardiac ablation, by determining the intralumen conductance and/or cross-sectional area at a plurality of locations within the body lumen.

PRIORITY

The present application is related to, claims the priority benefit of,and is a continuation application of, U.S. patent application Ser. No.12/305,520, filed Dec. 18, 2008, which is related to, claims thepriority benefit of, and is a § 371 application of, International PatentApplication Serial No. PCT/US2007/015239, filed Jun. 29, 2007, whichclaims priority to U.S. Provisional Patent Application Ser. No.60/817,422, filed Jun. 30, 2006, and which also claims priority to andis a continuation-in-part of U.S. patent application Ser. No.11/063,836, filed Feb. 23, 2005, which claims priority to U.S. patentapplication Ser. No. 10/782,149, filed Feb. 19, 2004, issued as U.S.Pat. No. 7,454,244, which claims priority to U.S. Provisional PatentApplication Ser. No. 60/449,266, filed Feb. 21, 2003, U.S. ProvisionalPatent Application Ser. No. 60/493,145, filed Aug. 7, 2003, and U.S.Provisional Patent Application Ser. No. 60/502,139, filed Sep. 11, 2003.The contents of each of these applications are hereby incorporated byreference in their entirety into this disclosure.

BACKGROUND

Atrial fibrillation (“AF”) of the human heart is a common arrhythmiawhich is estimated to affect anywhere from 2.2 million to about 5.1million Americans, as well as approximately 5% of the elderly populationover 69 years of age. Theoretically, the AF mechanism involves two mainprocesses: (1) higher automaticity in one or more rapidly depolarizingfoci and (2) reentry of conduction involving one or more circuits. Rapidatrial foci, often located in at least one of the superior pulmonaryveins, can begin AF in predisposed patients. In addition, the“multiple-wavelet hypothesis” has been proposed as a potential mechanismfor AF caused by conduction reentry. According to the hypothesis, normalconduction wave fronts break up, resulting in a number ofself-perpetuating “daughter” wavelets that spread through the atriacausing abnormal contraction of the myocardium.

Surgical treatment of AF requires the construction of barriers toconduction within the right atrium and left atrium to restrict theamount of myocardium available to spread reentrant wave fronts, therebyinhibiting sustained AF. By making incisions in the myocardium,conduction is interrupted. Since it has been demonstrated that thepulmonary veins often contain the specific rapidly-depolarizing loci,incisions encircling the pulmonary veins can help prevent AF. Similarly,potentially arrhythmogenic foci close to the pulmonary veins, as well asspecific atrial regions with the shortest refractory periods, may beisolated from the rest of the atria by strategically placed incisions.Although the risk of such surgery alone is typically less than 1%, theneed for median sternotomy and the use of cardiopulmonary bypass, aswell as a risk of short-term fluid retention, make this procedure lessthan ideal.

As an alternative to surgery, catheter ablation has evolved as astandard therapy for patients at high risk for ventricular andsupraventricular tachyarrhythmia. The recognition that foci triggeringAF frequently initiate within the pulmonary veins has led to ablationstrategies that target this zone or that electrically isolate thepulmonary veins from the left atrium. In the superior vena cava, theright atrium, left atrium, and coronary sinus were found as other sitesof arrhythmogenic foci. The frequency of recurrent AF has been reducedin more than 60% of patients by the ablation of the foci (superior venacava, the right and left atria, and the coronary sinus). However, therisk of recurrent AF following a focal ablation procedure is stillbetween 30% to 50% over the first year and is even higher when theablation involves an attempt to isolate more than one pulmonary vein.

In most circumstances, the cardiac ablation catheter is inserted into ablood vessel (artery or vein), usually through an entry site located inthe upper leg or neck. Under fluoroscopy, the tube is navigated throughthe blood vessels until it reaches the heart. In the heart, electrodesat the catheter tip gather data that pinpoint the location of faultytissue in the heart (electrical mapping). Once the site is identified,the device delivers either radiofrequency energy (RF ablation) orintense cold (cryoablation) to destroy the small section of tissue. Themajor goal of this procedure is segmental pulmonary vein isolation andcircumferential pulmonary vein ablation. The circumferential ablationstrategy yields either an atriovenous electrical disconnection, asdemonstrated by elimination of pulmonary vein ostial potentials andabsence of discrete electrical activity inside the lesion during pacingfrom outside the ablation line, or a profound atrial electroanatomicalremodeling as expressed by voltage abatement inside and around theencircled areas involving to some extent the posterior wall of the leftatrium. The endpoint is the electrical isolation of the pulmonary veinsfrom the left atrium, as they house foci triggering AF in about 80% toabout 95% of cases and seem to play a key role in arrhythmiamaintenance.

Possible complications of catheter ablation for AF include systemicembolism, pulmonary vein stenosis, pericardial effusion, cardiactamponade, and phrenic nerve paralysis. The majority of these risks stemfrom the ablation of an incorrect region. Hence, proper navigationduring cardiac ablation is one of the greatest challenges for theelectrophysiologist performing the procedure.

Visualization of endocardial structure and ablation lesions throughflowing blood has been an obstacle for proper navigation during cardiacablation. Currently, clinicians perform cardiac ablation usingintracardiac echo based on ultrasound. A catheter is advanced from thefemoral vein into the heart, thereby allowing the clinician to observethe heart from the inside. This method enables good anatomy imaging, andthe clinician can view the electrode-tissue interface during theablation. Despite this technology, however, the clinician cannot havecomplete certainty after the ablation procedure that the procedurecreated a permanent lesion that has destroyed only the targeted tissueand nothing more.

Another method used to determine the accuracy of the ablation is tocompare the electrical signals in the heart before and after theprocedure to determine whether certain arrhythmogenic signals have beeneliminated. However, this method does not always provide sufficientevidence that a permanent lesion has been created as a result of theablation.

Thus, these approaches fall short of providing optimum clarity andaccuracy regarding the ablation. Furthermore, conventional technologiesdo not combine the function of direct visualization and ablation intoone catheter, but instead require the use and coordination of multiplecatheters, thereby inherently increasing the risks to the patient.

A new technique has emerged that allows an electrophysiologist to createa real-time 3-D electroanatomical cardiac map using GPS-like technologycalled CARTO™ The created map is then merged with CT or MRI imagesproviding detailed structures of the chambers of the heart. Real-timeintracardiac echocardiography, along with fluoroscopy, is also used toenhance the safety and efficacy of the procedure. Another system, calledthe Localisa® Intracardiac Navigation System, allows a user tocontinuously monitor mapping and ablation catheter positions, thusfacilitating pulmonary vein isolation procedures and reducing radiationexposure to the patient and medical personnel.

Although these newer systems have significant potential, they aregenerally unavailable to the typical electrophysiology laboratorybecause of cost. Thus, there is a need for an efficient, easy to use,and reasonably priced technique for localization and ablation that canbe adapted for use in virtually any clinic.

BRIEF SUMMARY

Various embodiments of devices, systems, and methods for localization ofbody lumen junctures are disclosed herein. At least some of thedisclosed embodiments allow a clinician to identify a body lumenjunction, such as a pulmonary vein-atrial junction, or other desiredanatomical structures, to a higher spatial resolution than withconventional techniques. Thus, subsequent ablation may be performedusing the same device that presented a visual signal of the junction,thereby decreasing the tools required for proper location and ablationof the junction and targeted tissue.

Some embodiments disclosed herein include systems for localizing a bodylumen junction or other intraluminal structure. These systems comprise acatheter having a proximal end and a distal end for placement into abody lumen. The catheter may comprise a first electrode and a secondelectrode, and each of the first and second electrodes have a proximalend and a distal end; the distal ends of the first and second electrodesare located between the proximal and distal ends of the catheter. Thesystem further comprises a processor connected to the first and secondelectrodes of the catheter. The processor is capable of collectingconductance data to determine a profile of the body lumen. Theconductance data is collected at a plurality of locations within thebody lumen and determined at each of the plurality of locations when thedistal ends of the first and second electrodes are immersed in a fluidwithin the body lumen. In some embodiments, the processor is alsocapable of calculating a cross-sectional area of the body lumen at eachof the plurality of locations within the body lumen using theconductance data.

For certain embodiments of such systems, the relevant body lumencomprises at least a portion of an atrium, a pulmonary vein-atrialjunction, a blood vessel, a biliary tract, or an esophagus. Indeed, manyembodiments may be used in connection with any other body lumen that issuitable for access and localization.

The body lumen may have at least some fluid inside, and the fluid maycomprise blood or another suitable fluid, such as a solution of NaClhaving a known conductivity. Certain embodiments of the catheter have apassageway for passing fluid through the catheter to the location of thedistal ends of the first and second electrodes, such that the fluidpassing through the passageway comes in contact with the distal ends ofthe first and second electrodes. For some embodiments, the conductancedata is determined at each of a plurality of locations within the lumenwhen the distal ends of the first and second electrodes are immersed ina first fluid having a first conductivity and then a second fluid havinga second conductivity. The conductance data may comprise a firstconductance value determined at each of the plurality of locations whenthe distal ends of the first and second electrodes are immersed in thefirst fluid and a second conductance value determined at each of theplurality of locations when the distal ends of the first and secondelectrodes are immersed in the second fluid. The profile of the bodylumen is therefore determined from the first and second conductancevalues collected from each of the plurality of locations, the firstconductivity of the first fluid, and the second conductivity of thesecond fluid. The profile may consist of actual or relative values forcross-sectional areas or conductances.

Many embodiments disclosed herein have a catheter with at least fourelectrodes, including at least two excitation electrodes and at leasttwo detection electrodes. Each of the electrodes has a proximal end anda distal end, wherein the proximal ends of the electrodes may beconnected to the processor directly or indirectly. In at least someembodiments, the distal ends of the excitation electrodes are locatedbetween the proximal and distal ends of the catheter, and the distalends of the detection electrodes are located between the distal ends ofthe excitation electrodes.

Certain of the disclosed embodiments have at least one ablation contactpositioned at the distal end of the catheter, enabling the clinician toperform an ablation immediately following localization without having tochange catheters. The one or more ablation contacts are configured toremove or destroy a targeted tissue within the body lumen, such as byheating the tissue, freezing the tissue using cryoablation, mechanicallydestroying or removing the tissue, or by delivering an electrical chargeto the tissue. With respect to embodiments using electricity forablation, an adhesive grounding pad may be attached to the outside ofthe patient's body in order to conduct the electrical charge from thetargeted tissue.

The targeted tissue may include tissue that is located at, or adjacentto, a pulmonary vein-atrial junction. Such tissue may at least partiallysurround the junction, and may substantially surround the junction. Forproper location of the ablation, the ablation contact may be positionedcircumferentially around a substantially circular portion of thecatheter. In some embodiments the catheter includes more than oneablation contact.

Certain embodiments disclosed herein include a number of steps forlocalizing a junction or other structure within a body lumen, includingproviding an embodiment of a system as disclosed herein; introducing thecatheter into the body lumen; providing electrical current flow to thebody lumen through the catheter; measuring a first conductance value ata first location in the body lumen; moving the catheter to a secondlocation in the body lumen; measuring a second conductance value at asecond location in the body lumen; and determining a profile of the bodylumen based on the first conductance value of the first location and thesecond conductance value of the second location. The profile of the bodylumen resulting from such embodiments may include relative conductancesand/or relative cross-sectional areas.

For other embodiments, the actual values for the lumen conductance orcross-sectional area are determined by further injecting a known volumeof a first solution having a first conductivity into the body lumen;injecting a second solution having a second conductivity into the bodylumen, wherein the second solution has a second volume and wherein thesecond conductivity does not equal the first conductivity; measuring asecond conductance value at the first location in the body lumen;calculating the conductance at the first location in the body lumen;measuring a first conductance value at a second location in the bodylumen; and calculating the conductance at the second location in thebody lumen. The determination of the profile of the body lumen may bebased on the conductance of the first location, the conductance of thesecond location, and the conductivities of the first and secondsolutions. In addition, in some embodiments, the tissue is ablated afterlocalization using the same catheter for both aspects of the procedure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the visual output of an embodiment of a catheter system forlocalization during an experiment of movement through an interior of asurgical glove;

FIG. 2 shows the visual output of an embodiment of a catheter system forlocalization during an experiment of movement through an interior of aheart;

FIG. 3A shows an embodiment of a catheter for localization of a bodylumen juncture;

FIG. 3B shows another embodiment of a catheter for localization of abody lumen juncture;

FIG. 3C shows an embodiment of a catheter for localization and ablationof a body lumen juncture;

FIG. 4A shows another embodiment of a catheter for localization;

FIG. 4B shows an embodiment of a balloon catheter having impedancemeasuring electrodes supported in front of the stenting balloon;

FIG. 4C shows another embodiment of a balloon catheter having impedancemeasuring electrodes within and in front of the balloon;

FIG. 4D shows an embodiment of a catheter having an ultrasoundtransducer within and in front of the balloon;

FIG. 4E shows an embodiment of a guide catheter with wire and impedanceelectrodes;

FIG. 4F shows an embodiment of a catheter with multiple detectionelectrodes;

FIG. 5A shows an embodiment of a catheter in cross-section proximal tothe location of the sensors showing the leads embedded in the materialof the probe;

FIG. 5B shows another embodiment of a catheter in cross-section proximalto the location of the sensors showing the leads run in separate lumens;

FIG. 6 is a schematic of an embodiment of a system showing a cathetercarrying impedance measuring electrodes connected to a data processorequipment and excitation unit for the measurement of conductance and/orcross-sectional area;

FIG. 7A shows the detected filtered voltage drop as measured in theblood stream before and after injection of 1.5% NaCl solution;

FIG. 7B shows the peak-to-peak envelope of the detected voltage shown inFIG. 7A;

FIG. 8A shows the detected filtered voltage drop as measured in theblood stream before and after injection of 0.5% NaCl solution;

FIG. 8B shows the peak-to-peak envelope of the detected voltage shown inFIG. 8A;

FIG. 9 shows balloon distension of the lumen of the coronary artery;

FIG. 10 shows balloon distension of a stent into the lumen of thecoronary artery;

FIG. 11A shows the voltage recorded by a conductance catheter with aradius of 0.55 mm for various size vessels (vessel radii of 3.1, 2.7,2.3, 1.9, 1.5 and 0.55 mm for the six curves, respectively) when a 0.5%NaCl bolus is injected into the treatment site; and

FIG. 11B shows the voltage recorded by a conductance catheter with aradius of 0.55 nm for various size vessels (vessel radii of 3.1, 2.7,2.3, 1.9, 1.5 and 0.55 mm for the six curves, respectively) when a 1.5%NaCl bolus is injected into the treatment site.

DETAILED DESCRIPTION

It will be appreciated by those of skill in the art that the followingdetailed description of the disclosed embodiments is merely exemplary innature and is not intended to limit the scope of the appended claims.

During various medical procedures involving intraluminal insertion ofcatheters or other devices, proper navigation of the device through bodylumens, such as blood vessels or the heart, is critical to the successof the procedure. Indeed, unless the tissue targeted for treatment ordiagnosis during the procedure is properly located, the procedure can beineffective or, even worse, damaging to nearby healthy tissue.Therefore, a number of the embodiments disclosed herein permit aclinician to readily locate a catheter, such as an ablation catheter, orother medical device within a body lumen in relation to body lumenjunctions or other anatomical structures within the lumen. This leads toproper localization of targeted tissue and increased favorable outcomes.

Some of the disclosed embodiments measure electrical conductance withinthe body lumen and display a profile of relative conductance values,while other embodiments use conductance data to calculate luminalcross-sectional areas and display a profile of relative cross-sectionalareas along a portion of the lumen. These profiles enable the clinicianto readily locate the targeted tissue for further treatment, such asablation. In some embodiments, the conductance catheter and the ablationcatheter is combined into one device so that ablation can occurimmediately following localization, without requiring a change ofcatheters.

Many of the disclosed embodiments do not calculate an absolute value fora lumen's cross-sectional area, but instead measure electricalconductance through a portion of the lumen to form a profile of thelumen. Often, the profile comprises relative conductances taken alongthe lumen. However, because conductance is proportional tocross-sectional area, as explained herein, the profile can compriserelative cross-sectional areas that have been determined from theconductances taken along the lumen.

By monitoring the profile during catheterization, the clinician canvisualize the anatomical structure of the lumen. For example, using apush through or a pull back of a disclosed embodiment of a catheterthrough a lumen, a clinician is able to localize a junction or otherarchitectural marker in the body lumen. Such a push through or pull backwill reflect, in relative terms, the lumen's changes in conductance, andtherefore its changes in cross-sectional area, as the catheter moves,thereby depicting changes in lumen structure across a distance. Based onsuch changes in lumen structure, a clinician can determine the locationsof various anatomical markers of the lumen, as well as the location ofthe catheter in relation to those markers. For example, localization ofthe junction between the relatively small pulmonary veins and thesignificantly larger atrium is possible by assessing the change inconductance (and therefore in cross-sectional area) of the lumen as thecatheter is pushed through the vein into the atrium.

Once a specific lumen junction or other anatomical structure islocalized, the clinician can better treat a targeted tissue at or nearthat identifying structure. Such treatment may include, for example,ablation, localized drug delivery, angioplasty, or stent delivery. Onecommon use of ablation is to electrically isolate arrhythmogenic foci,which are often found in the superior pulmonary veins, from the leftatrium to prevent atrial fibrillation in at-risk patients. To isolatethe vein and prevent further arrhythmogenic conduction from the foci,the cardiac tissue surrounding the pulmonary vein at or adjacent to thepulmonary vein-atrial junction is ablated. Ablation can be performed ina number of ways, including mechanically, electrically, using heat, orusing cryoablation. Regardless of the method for removing or destroyingthe targeted tissue, the clinician preparing to ablate an area ofcardiac tissue surrounding a pulmonary vein must direct the ablationdevice, often a catheter configured for ablation, to the targeted tissuesurrounding the pulmonary vein-atrial junction.

Various devices, systems, and methods for localization of body lumenjunctures disclosed herein permit the clinician to accurately locate thepulmonary vein-atrial junction, as well as confirm the location of theablation catheter with respect to the junction (and, therefore, thetargeted tissue). Indeed, localization using the disclosed embodimentswill minimize undesired ablation into the pulmonary veins, which causesshrinkage of collagen and hence pulmonary vein stenosis. It will alsominimize the ablation of the atrium too far from the pulmonary vein,where the ablation circumference is too large and isolation ofconductance is unlikely.

Experiments have demonstrated the ability of the disclosed embodimentsto provide accurate and reliable feedback as to the location of acatheter within a body lumen. For instance, a surgical glove was filledwith saline to simulate a left atrium (the palm) and pulmonary veins(the fingers). A catheter configured for localization as describedherein was pulled back from inside a finger to the palm, therebysimulating the transition from a pulmonary vein to the atrium. FIG. 1shows the conductance profile 10 as the catheter was pulled back from afinger into the palm of the glove, then was pushed into a finger. As canbe seen, the profile shows that the conductance of the palm wassignificantly larger than the conductance of the finger, and thetransition or demarcation from the finger to the palm is apparent.Because conductance and cross-sectional area are proportional (asdiscussed below), conductance profile 10 is proportional to the CSAprofile (not shown) and distinguishes between the smallercross-sectional area of the fingers and the larger cross-sectional areaof the palm.

A similar pullback experiment was carried out in a heart. Starting fromthe pulmonary vein, a catheter configured for localization as describedherein was pulled back from the pulmonary vein into the left atrium andventricle. FIG. 2 shows a conductance tracing 12 that reflects theconductance for each region of the body lumen as the catheter is pulledback over a distance of about 5 cm from a starting point in thepulmonary vein. The pulmonary vein can be clearly identified byreference to its relative conductance compared to those of the leftatrium, the mitral valve, and the left ventricle. Indeed, the atrial CSAis significantly larger than that of the pulmonary vein, and the atrialCSA increases with distance away from the pulmonary vein-atrialjunction. A reduction in CSA is then observed as the catheter approachesand crosses the mitral valve. Once the catheter progresses through themitral valve into the ventricle, the CSA increases gradually.

Using conductance data like that shown in FIG. 2, a clinician is able tolocate the pulmonary vein-atrial junction, and then the tissue targetedfor ablation, using a localization and ablation catheter as disclosedherein. For instance, once the end of the pulmonary vein is identifiedusing the type of conductance data shown in FIG. 2 (i.e., where theconductance begins to increase), a 2 mm to 3 mm pullback will provide anappropriate region for ablation in most situations. The axial positionof the catheter can be determined by the velocity of the pullback. Theexact amount of necessary pullback should be determined by the clinicianon a case by case basis based on the size of the patient and otherrelevant factors.

A conductance or impedance catheter measures conductance within a bodylumen using a number of electrodes. Referring now to FIG. 3A, there isshown a conductance catheter 400 configured to localize a body lumenjunction using conductance measurements. Catheter 400 has a proximal end405 and a distal end 410, which is suitable for introduction into a bodylumen. In addition, catheter 400 includes a pair of excitationelectrodes 415 and a pair of detection electrodes 420. Each ofexcitation electrodes 415 and detection electrodes 420 has a proximalend that is capable of attachment to a processing system (not shown) anda distal end that is located on catheter 400 between proximal end 405and distal end 410. The distal ends of detection electrodes 420 arelocated on catheter 400 between the distal ends of excitation electrodes415. Excitation electrodes 415 are configured to emit a measuredelectrical charge into the body lumen, while detection electrodes 420detect the amount of the charge that travels through a fluid within thebody lumen. As explained in more detail below, a processing systemcalculates the change in electrical charge to determine the conductancethrough the lumen at any given location in the lumen.

As shown in FIG. 3A, electrodes 415 and 420 are located at distal end410 of catheter 400. However, the positioning of the electrodes is notlimited to this distal end portion, but may be anywhere on the catheterthat can assist in providing conductance information to the clinician.Furthermore, multiple sets of electrodes (see FIG. 4F) may also be usedto provide additional information used for mapping the interioranatomical structure of an internal organ, vessel, or other body lumen.

Many embodiments disclosed herein, such as the embodiment shown in FIG.3A, have at least two detection electrodes and two excitationelectrodes. However, in the embodiment shown in FIG. 3B, only twoelectrodes are used. Catheter 425 has a proximal end 430 and a distalend 435, as well as a first electrode 440 and a second electrode 445.Each of electrodes 440 and 445 has a proximal end (not shown) and adistal end located on catheter 425 between proximal end 430 and distalend 435. Because catheter 425 has only two electrodes, each electrodemust serve both the excitation function and the detection function. Toenable a single electrode to send and measure the electric charge, adelay must be added to the circuit. Additionally, a bipolar cathetermust be stationary at the time of measurement, requiring the clinicianto obtain a profile by moving the catheter to a desired location,stopping and taking a measurement, and then moving the catheter again.By contrast, tetrapolar catheters may take a continuous conductancemeasurement as the catheter is pulled or pushed through the body lumen,thereby giving a more detailed profile as compared to bipolar catheters.

Although the embodiments shown in FIG. 3A and FIG. 3B are used primarilyfor localization, certain of the disclosed embodiments combine thefunction of localization and ablation into one catheter and therebyimprove the accuracy and safety of the ablation procedure by allowingthe physician to properly identify the targeted tissue for ablationbefore the ablation begins. For example, catheter 450 shown in FIG. 3Cis a conductance catheter that is configured to both localize a bodylumen junction and ablate targeted tissue at or adjacent to thejunction. Catheter 450 has an ablation contact 460 for removing ordestroying a targeted tissue, two excitation electrodes 470, and twodetection electrodes 480, as well as a passageway 490 for passing fluidthrough catheter 450 to the body lumen. Each of excitation electrodes470 and detection electrodes 480 has a proximal end (not shown) forconnection to a processor and a distal end positioned on catheter 450.The distal ends of detection electrodes 480 are positioned on catheter450 between the distal ends of excitation electrodes 470.

Although at least some embodiments can properly measure lumenconductance in the presence of a bodily fluid (such as blood) within thelumen, certain other embodiments may use fluids injected into the bodylumen to properly calculate lumen conductance and/or cross-sectionalarea, as explained herein. Therefore, some embodiments include a channelthrough which fluid is injected into the body lumen. In the embodimentshown in FIG. 3C, infusion passageway 490 is configured to permit suchinjection so that fluid flowing from passageway 490 will flow at leastto the location of the distal ends of excitation electrodes 470 anddetection electrodes 480. Thus, the fluid passing through passageway 490into the lumen will come in contact with the distal ends of excitationelectrodes 470 and detection electrodes 480.

Referring again to FIG. 3C, ablation contact 460 delivers an electriccurrent to a tissue targeted for ablation. The current passes throughablation contact 460, which is in contact with the targeted tissue,entering the targeted tissue and returning to a grounding pad electrode500 that is positioned on the outside of the body. Grounding padelectrode 500 may be held in place using any acceptable means, includingan adhesive safe for contact with human skin. Although ablation contact460 uses electrical current to destroy targeted tissue, other types ofsuitable ablation methods may be used. For instance, other embodimentsdisclosed herein could ablate tissue using very high heat, mechanicalmeans, or cryoablation.

Referring now to FIGS. 4A to 4F, several embodiments of catheters areillustrated. With reference to the embodiment shown in FIG. 4A, there isshown an impedance catheter 22 with four electrodes 25, 26, 27, and 28placed close to distal end 19 of the catheter. Electrodes 25 and 27 areexcitation electrodes, while electrodes 26 and 28 are detectionelectrodes, thereby permitting measurement of conductance (and thereforecalculation of cross-sectional area) during advancement of the catheter,as described in further detail below.

In addition, catheter 22 possesses an optional infusion passageway 35located proximal to excitation electrode 25, as well as optional ports36 for suction of contents of the body lumen or for infusion of fluid.The fluid to inject through passageway 35 or ports 36 can be anybiologically compatible fluid, but, for some circumstances disclosedherein, the conductivity of the fluid is selected to be different fromthat of blood.

In various embodiments, including for example the embodiment shown inFIG. 4A, the catheter contains a channel 31 for insertion of a guidewire to stiffen the flexible catheter during insertion or datarecording. Additionally, channel 31 may be used to inject fluidsolutions of various concentrations (and various conductivities) intothe body lumen of interest. An additional channel 32 may be connected tothe catheter such that the electrical wires connected to the one or moreelectrodes on the catheter are directed through channel 32 and to a dataprocessor, such as data processor system 100 (see FIG. 6), through anadaptor interface 33, such as an impedance module plug or the like, asdescribed in more detail below.

In addition to localization and ablation, some embodiments disclosedherein provide other functionality. FIGS. 4B-4F show a number ofembodiments of conductance catheters having various functions. Forexample, several such embodiments include an angioplasty balloon, inaddition to impedance electrodes (see, e.g., FIG. 4B). Such cathetersmay include electrodes for accurate detection of organ luminalcross-sectional area and ports for pressure gradient measurements.Hence, when using such catheters, it is not necessary to changecatheters during the procedure, as with the current use of intravascularultrasound. In at least one embodiment, the catheter can provide directmeasurement of the non-stenosed area of the lumen, thereby allowing theselection of an appropriately sized stent for implantation.

With reference to the embodiment shown in FIG. 4B, four wires werethreaded through one of the two lumens of catheter 20 (a 4 Fr.catheter). Catheter 20 has a proximal end and a distal end 19, as wellas excitation electrodes 25, 27 and detection electrodes 26, 28 placedat or near distal end 19. Proximal to these electrodes is an angioplastyor stenting balloon 30 capable of being used to treat stenosis. Thedistance between the balloon and the electrodes is usually small, in the0.5 mm to 2 cm range, but can be closer or farther away, depending onthe particular application or treatment involved. The portion ofcatheter 20 within balloon 30 includes an infusion passageway 35 and apressure port 36.

Detection electrodes 26 and 28 are spaced 1 mm apart, while excitationelectrodes 25 and 27 are spaced 4 mm to 5 mm from either side of thedetection electrodes. The excitation and detection electrodes typicallysurround the catheter as ring electrodes, but they may also be pointelectrodes or have other suitable configurations. These electrodes maybe made of any conductive material, such as platinum iridium or amaterial with a carbon-coated surface to avoid fibrin deposits. In atleast one embodiment, the detection electrodes are spaced with 0.5 mm to1 mm between them and with a distance of between 4 mm and 7 mm to theexcitation electrodes on small catheters. On large catheters, for use inlarger vessels and other larger body lumens, the electrode distances maybe larger. The dimensions of the catheter selected for a treatmentdepend on the size of the vessel or other body lumen and are preferablydetermined in part on the results of finite element analysis.

In one approach, dimensions of a catheter to be used for any givenapplication depend on the optimization of the potential field usingfinite element analysis described below. For small organs or inpediatric patients, the diameter of the catheter may be as small as 0.3mm. In large organs, the diameter may be significantly larger dependingon the results of the optimization based on finite element analysis. Theballoon will typically be sized according to the preferred dimension ofthe organ after the distension. The balloon may be made of materialssuitable for the function, such as, for example, polyethylene, latex,polyestherurethane, or combinations thereof. The thickness of theballoon will typically be on the order of a few microns. The catheterwill typically be made of PVC or polyethylene, though other materialsmay be used equally well. The tip of the catheter can be straight,curved, or angled to facilitate insertion into the coronary arteries orother body lumens, such as, for example, the biliary tract.

Referring again to FIG. 4B, catheter 20 may also include severalminiature pressure transducers (not shown) carried by the catheter orpressure ports for determining the pressure gradient proximal to thesite where the conductance is measured. The pressure is preferablymeasured inside the balloon and proximal to, distal to, and at thelocation of the conductance measurement, and locations proximal anddistal thereto, thereby enabling the measurement of pressure recordingsat the site of stenosis and also the measurement of pressure-differencealong or near the stenosis. In one embodiment, shown in FIG. 4B,catheter 20 includes pressure port 90 and pressure port 91 proximal toor at the site of the conductance measurement for evaluation of pressuregradients. As described below with reference to FIGS. 5A, 5B, and 6, inat least one embodiment, the pressure ports are connected by respectiveconduits in catheter 20 to pressure sensors in the data processor system100 (see FIG. 6). Such pressure sensors are well known in the art andinclude, for example, fiber-optic systems, miniature strain gauges, andperfused low-compliance manometry.

In at least one embodiment, a fluid-filled silastic pressure-monitoringcatheter is connected to a pressure transducer. Luminal pressure can bemonitored by a low compliance external pressure transducer coupled tothe infusion channel of the catheter. Pressure transducer calibrationwas carried out by applying 0 and 100 mmHg of pressure by means of ahydrostatic column.

In another embodiment, shown in FIG. 4C, a catheter 39 includes anotherset of excitation electrodes 40, 41 and detection electrodes 42, 43located inside the angioplastic or stenting balloon 30 for accuratedetermination of the balloon cross-sectional area during angioplasty orstent deployment. These electrodes are in addition to electrodes 25, 26,27, and 28.

In various embodiments, the conductance may be measured using atwo-electrode system (see FIG. 4D). In other embodiments, such asillustrated in FIG. 4F, the conductances at several locations can bemeasured at the same time using an array of five or more electrodes.Here, excitation electrodes 51, 52 are used to generate the currentwhile detection electrodes 53, 54, 55, 56, and 57 are used to detect thecurrent at their respective sites.

In another embodiment, shown in FIG. 4D, catheter 21 has one or moreimaging or recording devices, such as, for example, ultrasoundtransducers 50 for cross-sectional area and wall thickness measurements.As shown, transducers 50 are located near distal end 19 of catheter 21.

With reference to the embodiment shown in FIG. 4E, electrodes 25, 26,27, and 28 are built onto a wire 18, such as, for example, a pressurewire, and inserted through a guide catheter 23, where the infusion of abolus can be made through the lumen of the guide catheter. Adaptorinterface 33 may be used to house and guide the electrical wires(including proximal portions of the excitation and detection electrodes)to a data processor system 100, while a side channel 34 is used toinject various fluids into catheter 23. In yet another embodiment (notillustrated), the catheter includes a sensor for measurement of the flowof fluid in the body lumen.

Referring now to the embodiment shown in FIG. 9, an angioplasty balloon30 is shown distended within a coronary artery 150 for the treatment ofstenosis. As described above with reference to FIG. 4C, a set ofexcitation electrodes 40, 41 and detection electrodes 42, 43 are locatedwithin angioplasty balloon 30. In another embodiment, shown in FIG. 10,angioplasty balloon 30 is used to distend a stent 160 within bloodvessel 150.

Many of the embodiments described herein may be used as part of asystem, which includes suitable connections between the system's variousparts. As described below with reference to FIGS. 5A, 5B, and 6, theexcitation and detection electrodes are electrically connected toelectrically conductive leads in the catheter for connecting theelectrodes to the data processor system 100.

FIGS. 5A and 5B illustrate in cross-section two embodiments 20A and 20Bof a catheter such as catheter 20 shown in FIG. 4B. Each embodiment hasa lumen 60 for inflating and deflating the balloon and a lumen 61 forsuction and infusion. The sizes of these lumens can vary. The electrodeleads 70A are embedded in the material of the catheter in the embodimentshown in FIG. 5A, whereas the electrode leads 70B are tunneled through alumen 71 formed within the body of catheter 20B shown in FIG. 5B.

Pressure conduits for perfusion manometry connect pressure ports 90, 91to transducers included in the data processor system 100. As shown inFIG. 5A, pressure conduits 95A may be formed in catheter 20A. In anotherembodiment, shown in FIG. 5B, pressure conduits 95B constituteindividual conduits within a tunnel 96 formed in catheter 20B. In theembodiments described above where miniature pressure transducers arecarried by the catheter, electrical conductors may be substituted forthese pressure conduits.

With reference to FIG. 6, in at least some embodiments, catheter 20connects to a data processor system 100, to a manual or automatic system105 for distension of the balloon, and to a system 106 for infusion offluid or suction of blood or other bodily fluid. The fluid for infusionmay be heated with heating unit 107 to between 37° C. and 39° C. or tobody temperature. The impedance planimetry system typically includes aconstant current unit, amplifiers, and signal conditioners, butvariations are possible. The pressure system typically includesamplifiers and signal conditioners. The system can optionally containsignal conditioning equipment for recording of fluid flow in the bodylumen.

In at least one embodiment, the system is pre-calibrated and a catheteris available in a package. The package also may contain sterile syringeswith fluids to be injected. The syringes are attached to the machine,and after heating of the fluid by the machine and placement of thecatheter in the body lumen of interest, the user presses a button thatinitiates the injection with subsequent computation of the desiredparameters. The CSA, parallel conductance, and/or other relevantmeasures, such as distensibility, tension, etc., will typically appearon the display panel in the PC module 160. The user can then remove thestenosis by distension or by placement of a stent.

If more than one CSA is measured at the same time, the system cancontain a multiplexer unit or a switch between CSA channels. In at leastone embodiment, each CSA measurement or pressure measurement will bethrough separate amplifier units.

In at least one embodiment, the impedance and pressure data are analogsignals which are converted by analog-to-digital converters 150 andtransmitted to a computer 160 for on-line display, on-line analysis, andstorage. In other embodiments, all data handling is done on an entirelyanalog basis.

The processor system includes software programs for analyzing theconductance data. Additional software calculates cross-sectional areasbased on a number of categories of data, as disclosed herein. However,as discussed in more detail below, to calculate for absolutecross-sectional values, certain errors must be reduced or eliminated.The software can be used to reduce the error in CSA values due toconductance of current in the lumen wall and surrounding tissue and todisplay the two-dimensional or three-dimensional geometry of the CSAdistribution along the length of the vessel (and, optionally, along withthe pressure gradient). In one embodiment of the software, a finiteelement approach or a finite difference approach is used to derive theCSA of organ stenosis, taking parameters such as conductivities of thefluid in the lumen and of the lumen wall and surrounding tissue intoconsideration.

In another embodiment, simpler circuits are used. As explained herein,absolute cross-sectional values may be calculated based on two or moreinjections of different NaCl solutions, which varies the conductivity offluid in the lumen. In other embodiments, the software contains the codefor reducing the error in luminal CSA measurement by analyzing signalsduring interventions, such as infusion of a fluid into the lumen or bychanging the amplitude or frequency of the current from the currentamplifier. The software chosen for a particular application may allowfor computation of the CSA with only a small error instantly or withinacceptable time during the medical procedure.

Referring now to FIG. 4A, catheter 22 measures conductance in the bodylumen by detecting the change in voltage between detection electrodes26, 28, as shown by the following equation:

$\begin{matrix}{{\Delta\; V} = \frac{I \cdot L}{C \cdot {CSA}}} & \left\lbrack {1a} \right\rbrack\end{matrix}$

Thus, the change in voltage, ΔV, is equal to the magnitude of thecurrent, I, multiplied by the distance between the detection electrodes,L, divided by the conductivity of the fluid in the lumen, C, and dividedby the cross-sectional area, CSA. Because the current (I), the distance(L), and the conductivity (C) normally can be regarded as calibrationconstants during a localization procedure, an inversely proportionalrelationship exists between the voltage difference and the CSA, as shownby the following equation:

$\begin{matrix}{{\Delta\; V} = \frac{1}{CSA}} & \left\lbrack {1b} \right\rbrack\end{matrix}$In other words, as the cross-sectional area of the lumen decreases, thechange in voltage measured by catheter 22 increases. As discussedearlier, conductance and cross-sectional area are proportional. Thus,this equation permits the relative conductances or cross-sectional areasof various intralumen anatomical structures to be determined frommeasurement of the change in voltage across the lumen using at least oneexcitation electrode and one detection electrode.

This measurement, however, does not produce accurate, or absolute,values of conductance or cross-sectional area because of the loss ofcurrent in the wall of the lumen and surrounding tissue. Althoughrelying on the relative conductances or cross-sectional areas issufficient for the localization of intraluminal structures, otherembodiments for other purposes may require the accurate determination ofabsolute values for cross-sectional areas.

For example, accurate measures of the luminal cross-sectional area oforgan stenosis within acceptable limits enables accurate and scientificstent sizing and placement. Proper stent implantation improves clinicaloutcomes by avoiding under or over deployment and under or over sizingof a stent, which can cause acute closure or in-stent re-stenosis. In atleast one embodiment disclosed herein, an angioplasty or stent balloonincludes impedance electrodes supported by the catheter in front of theballoon. These electrodes enable the immediate determination of thecross-sectional area of the vessel during the balloon advancement. Thisprovides a direct measurement of non-stenosed area and allows theselection of the appropriate stent size. In one approach, error due tothe loss of current in the wall of the organ and surrounding tissue iscorrected by injection of two solutions of NaCl or other solutions withknown conductivities. In another embodiment, impedance electrodes arelocated in the center of the balloon in order to deploy the stent to thedesired cross-sectional area. These embodiments and proceduressubstantially improve the accuracy of stenting and the outcome of suchstenting, as well as reduce overall costs.

Other embodiments make diagnosis of valve stenosis more accurate andmore scientific by providing a direct, accurate measurement ofcross-sectional area of the valve annulus, independent of the flowconditions through the valve. Thus, in such embodiments, the excitationand detection electrodes are embedded within a catheter to measure thevalve area directly, independent of cardiac output or pressure drop, andtherefore errors in the measurement of valve area are minimized.Further, pressure sensors may be mounted proximal and distal to theimpedance electrodes to provide simultaneous pressure gradientrecording.

Other embodiments improve evaluation of cross-sectional area and flow inorgans like the gastrointestinal tract and the urinary tract

At least some of the disclosed embodiments overcome the problemsassociated with determination of the size (cross-sectional area) ofluminal organs, such as, for example, in the coronary arteries, carotid,femoral, renal and iliac arteries, aorta, gastrointestinal tract,urethra, and ureter. In addition, at least some embodiments also providemethods for registration of acute changes in wall conductance, such as,for example, due to edema or acute damage to the tissue, and fordetection of muscle spasms/contractions.

The operation of catheter 20, shown in FIG. 4B, is as follows: forelectrodes 25, 26, 27, 28, conductance of current flow through the organlumen and organ wall and surrounding tissue is parallel; i.e.,

$\begin{matrix}{{G\left( {z,t} \right)} = {\frac{{{CSA}\left( {z,t} \right)} \cdot C_{b}}{L} + {G_{p}\left( {z,t} \right)}}} & \left\lbrack {2a} \right\rbrack\end{matrix}$where G_(p)(z,t) is the effective conductance of the structure outsidethe bodily fluid (organ wall and surrounding tissue); C_(b) is thespecific conductivity of the bodily fluid, which for blood generallydepends on the temperature, hematocrit and orientation and deformationof blood cells; and L is the distance between the detection electrodes.This equation shows that conductance, G(z,t), is proportional to thecross-sectional area, CSA(z,t). Thus, a larger conductance will reflecta larger cross-sectional area, and vice versa.

Equation [2a] can be rearranged to solve for cross sectional areaCSA(z,t), with a correction factor, α, if the electric field isnon-homogeneous, as

$\begin{matrix}{{{CSA}\left( {z,t} \right)} = {\frac{L}{\alpha\; C_{b}}\left\lbrack {{G\left( {z,t} \right)} - {G_{p}\left( {z,t} \right)}} \right\rbrack}} & \left\lbrack {2b} \right\rbrack\end{matrix}$where α would be equal to 1 if the field were completely homogeneous.The parallel conductance, G_(p), is an offset error that results fromcurrent leakage. G_(p) would equal 0 if all of the current were confinedto the blood and hence would correspond to the cylindrical model givenby Equation [1a]. In one approach, finite element analysis is used toproperly design the spacing between detection and excitation electrodesrelative to the dimensions of the body lumen to provide a nearlyhomogenous field such that a can be considered equal to 1. Simulationsshow that a homogenous or substantially homogenous field is provided by(1) the placement of detection electrodes substantially equidistant fromthe excitation electrodes and (2) maintaining the distance between thedetection and excitation electrodes substantially comparable to the bodylumen diameter. In one approach, a homogeneous field is achieved bytaking steps (1) and/or (2) described above so that α is equals 1 in theforegoing analysis.

G_(p) is a constant at any given position, z, along the long axis of abody lumen, and at any given time, t, in the cardiac cycle. Hence, twoinjections of different concentrations (and therefore conductivities) ofNaCl solution give rise to two equations:C ₁·CSA(z,t)+L·G _(p)(z,t)=L·G _(p)(z,t)  [3]andC ₂·CSA(z,t)+L·G _(p)(z,t)=L·G ₂(z,t)  [4]which can be solved simultaneously for CSA and G_(p) as

$\begin{matrix}{{{{CSA}\left( {z,t} \right)} = {L\frac{\left\lbrack {{G_{2}\left( {z,t} \right)} - {G_{1}\left( {z,t} \right)}} \right\rbrack}{\left\lbrack {C_{2} - C_{1}} \right\rbrack}}}{and}} & \lbrack 4\rbrack \\{{G_{p}\left( {z,t} \right)} = \frac{\left\lbrack {{C_{2} \cdot {G_{1}\left( {z,t} \right)}} - {C_{1} \cdot {G_{2}\left( {z,t} \right)}}} \right\rbrack}{\left\lbrack {C_{2} - C_{1}} \right\rbrack}} & \lbrack 5\rbrack\end{matrix}$where subscript “1” and subscript “2” designate any two injections ofdifferent NaCl concentrations (and conductivities). For each injectionk, C_(k) gives rise to G_(k) which is measured as the ratio of the rootmean square of the current divided by the root mean square of thevoltage. The C_(k) is typically determined through in vitro calibrationfor the various NaCl concentrations. The concentration of NaCl used istypically on the order of 0.45 to 1.8%. The volume of NaCl solution istypically about 5 ml, but the amount of solution should be sufficient tomomentarily displace the entire local vascular blood volume or otherbody lumen fluid. The values of CSA(t) and G_(p)(t) can be determined atend-diastole or end-systole (i.e., the minimum and maximum values) orthe mean thereof. The value of CSA would vary through the cardiac cycle,but G_(p)(t) does not vary significantly.

Once the CSA and G_(p) of the body lumen are determined according to theabove embodiment, rearrangement of Equation [2a] allows the calculationof the specific electrical conductivity of bodily fluid in the presenceof fluid flow as

$\begin{matrix}{C_{b} = {\frac{L}{{CSA}\left( {z,t} \right)}\left\lbrack {{G\left( {z,t} \right)} - {G_{p}\left( {z,t} \right)}} \right\rbrack}} & \lbrack 7\rbrack\end{matrix}$In this way, Equation [2b] can be used to calculate the CSA continuously(temporal variation, as for example through the cardiac cycle) in thepresence of bodily fluid.

In one approach, a pull or push through is used to reconstruct the bodylumen CSA along its length. During a long injection (e.g., 10 s to 15s), the catheter can be pulled back or pushed forward at constantvelocity, U. Equation [2a] can be expressed as

$\begin{matrix}{{{CSA}\left( {{U \cdot t},t} \right)} = {\frac{L}{C_{b}}\left\lbrack {{G\left( {{U \cdot t},t} \right)} - {G_{p}\left( {U \cdot \left( {t,t} \right)} \right\rbrack}} \right.}} & \lbrack 8\rbrack\end{matrix}$where the axial position, z, is the product of catheter velocity, U, andtime, t; i.e., z=U·t.

For the two injections, denoted by subscript “1” and subscript “2”,respectively, different time points T₁, T₂, etc., may be considered suchthat Equation [8] can be written as

$\begin{matrix}{{{CSA}_{1}\left( {{U \cdot T_{1}},t} \right)} = {\frac{L}{C_{1}}\left\lbrack {{G_{1}\left( {{U \cdot T_{1}},t} \right)} - {G_{p\; 1}\left( {{U \cdot T_{1}},t} \right)}} \right\rbrack}} & \left\lbrack {9a} \right\rbrack \\{{{CSA}_{1}\left( {{U \cdot T_{1}},t} \right)} = {\frac{L}{C_{2}}\left\lbrack {{G_{2}\left( {{U \cdot T_{1}},t} \right)} - {G_{p\; 1}\left( {{U \cdot T_{1}},t} \right)}} \right\rbrack}} & \left\lbrack {9b} \right\rbrack \\{{{CSA}_{2}\left( {{U \cdot T_{2}},t} \right)} = {\frac{L}{C_{1}}\left\lbrack {{G_{1}\left( {{U \cdot T_{2}},t} \right)} - {G_{p\; 2}\left( {{U \cdot T_{2}},t} \right)}} \right\rbrack}} & \left\lbrack {10a} \right\rbrack \\{{{CSA}_{2}\left( {{U \cdot T_{2}},t} \right)} = {\frac{L}{C_{2}}\left\lbrack {{G_{2}\left( {{U \cdot T_{2}},t} \right)} - {G_{p\; 2}\left( {{U \cdot T_{2}},t} \right)}} \right\rbrack}} & \left\lbrack {10b} \right\rbrack\end{matrix}$and so on. Each set of Equations [9a], [9b] and [10a], [10b], etc. canbe solved for CSA₁, G_(p1) and CSA₂, G_(p2), respectively. Hence, onecan measure the CSA at various time intervals and therefore at differentpositions along the body lumen to reconstruct the length of the lumen.In at least one embodiment, the data on the CSA and parallel conductanceas a function of longitudinal position along the body lumen can beexported from an electronic spreadsheet, such as, for example, aMicrosoft Excel file, to diagramming software, such as AutoCAD®, wherethe software uses the coordinates to render a three-dimensionaldepiction of the lumen on the monitor.

For example, in one exemplary approach, the pull back reconstruction wasmade during a long injection where the catheter was pulled back atconstant rate by hand. The catheter was marked along its length suchthat the pull back was made at 2 mm/sec. Hence, during a 10-secondinjection, the catheter was pulled back about 2 cm. The data wascontinuously measured and analyzed at every two second interval; i.e.,at every 4 mm. Thus, six different measurements of CSA and G_(p) weretaken which were used to reconstruct the CSA and G_(p) along the lengthof the 2 cm segment.

In one approach, the wall thickness is determined from the parallelconductance for those body lumens that are surrounded by air ornon-conducting tissue. In such cases, the parallel conductance is equalto

$\begin{matrix}{G_{p} = \frac{{CSA}_{w} \cdot C_{w}}{L}} & \left\lbrack {11a} \right\rbrack\end{matrix}$where CSA_(w) is the CSA of the lumen wall and C_(w) is the electricalconductivity of the wall. This equation can be solved for CSA_(w) as

$\begin{matrix}{{CSA}_{w} = \frac{G_{p} \cdot L}{C_{w}}} & \left\lbrack {11b} \right\rbrack\end{matrix}$

For a cylindrical body lumen, the wall thickness, h, can be expressed as

$\begin{matrix}{h = \frac{{CSA}_{w}}{\pi\; D}} & \lbrack 12\rbrack\end{matrix}$where D is the diameter of the lumen, which can be determined from thecircular CSA(D=[4CSA/π]^(1/2)).When the CSA, pressure, wall thickness, and flow data are determinedaccording to the embodiments outlined above, it is possible to computethe compliance (e.g., ΔCSA/ΔP), tension (e.g., P*r, where P and r arethe intraluminal pressure and radius of a cylindrical organ), stress(e.g., P*r/h where h is the wall thickness of the cylindrical organ),strain (e.g., (C−C_(d))/C_(d) where C is the inner circumference andC_(d) is the circumference in diastole) and wall shear stress (e.g., 4μQ/r³ where μ, Q and r are the fluid viscosity, flow rate and radius ofthe cylindrical organ, respectively, for a fully developed flow). Thesequantities can be used in assessing the mechanical characteristics ofthe system in health and disease.

In at least one approach for localization or measuring the conductance(and determining the cross-sectional area) of a body lumen, a catheteris introduced from an exteriorly accessible opening (for example, themouth, nose, or anus for GI applications, or the mouth or nose forairway applications) into the targeted body lumen. For cardiovascularapplications, the catheter can be inserted into the lumens in variousways, such as, for example, those used in conventional angioplasty. Inat least one embodiment, an 18 gauge needle is inserted into the femoralartery followed by an introducer. A guide wire is then inserted into theintroducer and advanced into the lumen of the femoral artery. A 4 or 5Fr. conductance catheter is then inserted into the femoral artery viawire, and the wire is subsequently retracted. The catheter tipcontaining the conductance electrodes can then be advanced to the regionof interest by use of x-ray (e.g., fluoroscopy). In another approach,this methodology is used on small to medium size vessels (e.g., femoral,coronary, carotid, iliac arteries).

In at least one example of a clinical application, obtaining an accuratemeasurement (within acceptable limits) of the luminal cross-sectionalarea of an aortic aneurysm enables accurate and scientific stent sizingand placement. Proper stent implantation improves clinical outcomes byavoiding under or over deployment and under or over sizing of a stent,which can cause acute closure or in-stent re-stenosis. In at least oneembodiment, an angioplasty or stent balloon includes impedanceelectrodes supported by the catheter in front of the balloon. Asdescribed herein, these electrodes enable the immediate, or real-timedetermination of the cross-sectional area of the vessel during theballoon advancement. This provides a direct measurement of non-stenosedarea and allows for the appropriate stent size to be selected. In oneapproach, impedance electrodes are located in the center of the balloonin order to deploy the stent to the desired cross-sectional area. Suchembodiments and procedures substantially improve the accuracy ofstenting and the outcome of such stenting, as well as reduce overallcosts.

In one approach, a minimum of two injections with differentconcentrations of NaCl (and, therefore, different conductivities) arerequired to solve for the two unknowns, CSA and G_(p). However, in otherembodiments disclosed herein, only relative values for conductance orcross-sectional area are necessary, so the injection of two solutions isnot necessary. In another approach, three injections will yield threesets of values for CSA and G_(p) (although not necessarily linearlyindependent), while four injections would yield six sets of values. Inone approach, at least two solutions (e.g., 0.5% and 1.5% NaClsolutions) are injected in the targeted vessel or other lumen. Studiesindicate that an infusion rate of approximately 1 ml/s for a five secondinterval is sufficient to displace the blood volume and results in alocal pressure increase of less than 10 mmHg in the coronary artery.This pressure change depends on the injection rate which should becomparable to the lumen flow rate.

In at least one approach, involving the application of Equations [5] and[6], the vessel is under identical or very similar conditions during thetwo injections. Hence, some variables, such as the infusion rate, bolustemperature, etc., are similar for the two injections. Typically, ashort time interval is to be allowed (1 to 2 minute period) between thetwo injections to permit the vessel to return to homeostatic state. Thiscan be determined from the baseline conductance as shown in FIG. 7A, 7B,8A, or 8B. The parallel conductance is preferably the same or verysimilar during the two injections. Dextran, albumin, or another largemolecular weight molecule may be added to the NaCl solutions to maintainthe colloid osmotic pressure of the solution to reduce or prevent fluidor ion exchange through the vessel wall.

In one approach, the NaCl solution is heated to body temperature priorto injection since the conductivity of current is temperature dependent.In another approach, the injected bolus is at room temperature, but atemperature correction is made since the conductivity is related totemperature in a linear fashion.

In one approach, a sheath is inserted through either the femoral arteryor the carotid artery in the direction of flow. To access the loweranterior descending (“LAD”) artery, the sheath is inserted through theascending aorta. For the carotid artery, where the diameter is typicallyon the order of 5 mm to 5.5 mm, a catheter having a diameter of 1.9 mmcan be used, as determined from finite element analysis, discussedfurther below. For the femoral and coronary arteries, where the diameteris typically in the range from 3.5 mm to 4 mm, so a catheter of about0.8 mm diameter would be appropriate. The catheter can be inserted intothe femoral, carotid, or LAD artery through a sheath appropriate for theparticular treatment. Measurements for all three vessels can be madesimilarly.

Described here are the protocol and results for one approach that isgenerally applicable to most arterial vessels. The conductance catheterwas inserted through the sheath for a particular vessel of interest. Abaseline reading of voltage was continuously recorded. Two containerscontaining 0.5% and 1.5% NaCl were placed in temperature bath andmaintained at 37° C. A 5 ml to 10 ml injection of 1.5% NaCl was madeover a 5 second interval. The detection voltage was continuouslyrecorded over a 10 second interval during the 5 second injection.Several minutes later, a similar volume of 1.5% NaCl solution wasinjected at a similar rate. The data was again recorded. Matlab® wasused to analyze the data including filtering with high pass and with lowcut off frequency (1200 Hz). The data was displayed using Matlab®, andthe mean of the voltage signal during the passage of each respectivesolution was recorded. The corresponding currents were also measured toyield the conductance (G=I/V). The conductivity of each solution wascalibrated with six different tubes of known CSA at body temperature. Amodel using Equation [1a] was fitted to the data to calculateconductivity C. The analysis was carried out with SPSS statisticalsoftware using the non-linear regression fit. Given C and G for each ofthe two injections, an Excel spreadsheet file was formatted to calculatethe CSA and G_(p) as per equations [5] and [6], respectively. Thesemeasurements were repeated several times to determine thereproducibility of the technique. The reproducibility of the data waswithin 5%. Ultrasound was used to measure the diameter of the vesselsimultaneous with our conductance measurements. The detection electrodeswere visualized with ultrasound, and the diameter measurements was madeat the center of the detection electrodes. The maximum differencesbetween the conductance and ultrasound measurements were within 10%.

FIGS. 7A, 7B, 8A, and 8B illustrate voltage measurements in the bloodstream in the left carotid artery. Here, the data acquisition had asampling frequency of 75 KHz, with two channels—the current injected andthe detected voltage, respectively. The current injected has a frequencyof 5 KHz, so the voltage detected, modulated in amplitude by theimpedance changing through the bolus injection, will have a spectrum inthe vicinity of 5 KHz.

With reference to FIG. 7A there is shown a signal processed with a highpass filter with low cut off frequency (1200 Hz). The top and bottomportions 200, 202 show the peak-to-peak envelope detected voltage whichis displayed in FIG. 7B. The initial 7 seconds correspond to thebaseline; i.e., electrodes in the blood stream. The next 7 secondscorrespond to an injection of hyper-osmotic NaCl solution (1.5% NaCl).It can be seen that the voltage is decreased, implying increasedconductance (since the injected current is constant). Once the NaClsolution is washed out, the baseline is recovered as shown in FIGS. 7Aand 7B. FIGS. 8A and 8B show similar data corresponding to 0.5% NaClsolutions.

The voltage signals are ideal since the difference between the baselineand the injected solution is apparent and systematic. Furthermore, thepulsation of vessel diameter can be seen in the 0.5% and 1.5% NaClinjections (FIGS. 7A, 7B and 8A, 8B, respectively). This allowsdetermination of the variation of CSA throughout the cardiac cycle asoutline above.

The NaCl solution can be injected by hand or by using a mechanicalinjector to momentarily displace the entire volume of blood or bodilyfluid in the lumen segment of interest. For example, in a blood vessel,the pressure generated by the injection will not only displace the bloodin the antegrade direction (in the direction of blood flow) but also inthe retrograde direction (by momentarily pushing the blood backwards).In other visceral organs which may be normally collapsed, the NaClsolution will not displace blood as in the vessels but will merely openthe organs and create a flow of the fluid. In one approach, afterinjection of a first solution into the treatment or measurement site,sensors monitor and confirm baseline of conductance prior to injectionof a second solution into the treatment site.

The injections described above are preferably repeated at least once toreduce errors associated with the administration of the injections, suchas, for example, where the injection does not completely displace theblood or where there is significant mixing with blood. It will beunderstood that any bifurcation(s) (with branching angle near 90degrees) near the targeted lumen can cause an overestimation of thecalculated CSA. Hence, generally the catheter should be slightlyretracted or advanced and the measurement repeated. An additionalapplication with multiple detection electrodes or a pull back or pushforward during injection will accomplish the same goal. Here, an arrayof detection electrodes can be used to minimize or eliminate errors thatwould result from bifurcations or branching in the measurement ortreatment site.

In one approach, error due to the eccentric position of the electrode orother imaging device can be reduced by inflation of a balloon on thecatheter. The inflation of the balloon during measurement will place theelectrodes or other imaging device in the center of the vessel away fromthe wall. In the case of impedance electrodes, the inflation of theballoon can be synchronized with the injection of a bolus such that theballoon inflation would immediately precede the bolus injection. Ourresults, however, show that the error due to catheter eccentricity issmall.

The CSA predicted by Equation [5] corresponds to the area of the vesselor other lumen external to the catheter (i.e., CSA of vessel minus CSAof catheter). If the conductivity of the NaCl solutions is determined bycalibration from Equation [1a] with various tubes of known CSA, then thecalibration accounts for the dimension of the catheter and thecalculated CSA corresponds to that of the total vessel lumen. In atleast one embodiment, the calibration of the CSA measurement system willbe performed at 37° C. by applying 100 mmHg in a solid polyphenolenoxideblock with holes of known CSA ranging from 7.065 mm² (3 mm in diameter)to 1017 mm² (36 mm in diameter). If the conductivity of the solutions isobtained from a conductivity meter independent of the catheter, however,then the CSA of the catheter is generally added to the CSA computed fromEquation [5] to give the total CSA of the vessel.

The signals are generally non-stationary, nonlinear, and stochastic. Todeal with non-stationary stochastic functions, one can use a number ofmethods, such as the Spectrogram, the Wavelet's analysis, theWigner-Ville distribution, the Evolutionary Spectrum, Modal analysis, orthe intrinsic model function (“IMF”) method. The mean or peak-to-peakvalues can be systematically determined by the aforementioned signalanalysis and used in Equation [5] to compute the CSA.

For the determination of conductance or cross-sectional area of a heartvalve, it is generally not feasible to displace the entire volume of theheart. Hence, the conductivity of the blood is transiently changed byinjection of a hypertonic NaCl solution into the pulmonary artery. Ifthe measured total conductance is plotted versus blood conductivity on agraph, the extrapolated conductance at zero conductivity corresponds tothe parallel conductance. In order to ensure that the two innerelectrodes are positioned in the plane of the valve annulus (2 mm to 3mm), in one embodiment, two pressure sensors 36 are placed immediatelyproximal and distal to (1 mm to 2 mm above and below, respectively) thedetection electrodes or sets of detection electrodes (see, e.g., FIGS.4A and 4F). The pressure readings will then indicate the position of thedetection electrode relative to the desired site of measurement (aorticvalve: aortic-ventricular pressure; mitral valve: leftventricular-atrial pressure; tricuspid valve: right atrial-ventricularpressure; pulmonary valve: right ventricular-pulmonary pressure). Theparallel conductance at the site of annulus is generally expected to besmall since the annulus consists primarily of collagen, which has lowelectrical conductivity. In another application, a pull back or pushforward through the heart chamber will show different conductance due tothe change in geometry and parallel conductance. This can be establishedfor normal patients, which can then be used to diagnose valvularstenosis.

In one approach, for the esophagus or the urethra, the procedures canconveniently be done by swallowing fluids of known conductivities intothe esophagus and infusion of fluids of known conductances into theurinary bladder followed by voiding the volume. In another approach,fluids can be swallowed or urine voided followed by measurement of thefluid conductivities from samples of the fluid. The latter method can beapplied to the ureter where a catheter can be advanced up into theureter and fluids can be injected from a proximal port on the probe(will also be applicable in the intestines) or urine production can beincreased and samples taken distal in the ureter during passage of thebolus or from the urinary bladder.

In one approach, concomitant with measuring the conductance,cross-sectional area, and/or pressure gradient at the treatment ormeasurement site, a mechanical stimulus is introduced by way ofinflating the balloon or by releasing a stent from the catheter, therebyfacilitating flow through the stenosed part of the lumen. In anotherapproach, concomitant with measuring the conductance, cross-sectionalarea, and/or pressure gradient at the treatment site, one or morepharmaceutical substances for diagnosis or treatment of stenosis isinjected into the treatment site. For example, in one approach, theinjected substance can be a smooth muscle agonist or antagonist. In yetanother approach, concomitant with measuring the conductance,cross-sectional area, and/or pressure gradient at the treatment site, aninflating fluid is released into the treatment site for release of anystenosis or materials causing stenosis in the lumen or treatment site.

Again, it will be noted that the methods, systems, and cathetersdescribed herein can be applied to any body lumen or treatment site. Forexample, the methods, systems, and catheters described herein can beapplied to any one of the following hollow bodily systems: thecardiovascular system including the heart; the digestive system; therespiratory system; the reproductive system; and the urogenital tract.

Finite Element Analysis: In one preferred approach, finite elementanalysis (FEA) is used to verify the validity of Equations [5] and [6].There are two major considerations for the model definition: geometryand electrical properties. The general equation governing the electricscalar potential distribution, V, is given by Poisson's equation as:∇·(C∇V)=−I  [13]where C, I, and ∇ are the conductivity, the driving current density, andthe del operator, respectively. Femlab or any standard finite elementpackage can be used to compute the nodal voltages using Equation [13].Once V has been determined, the electric field can be obtained fromE=−∇V.

The FEA allows the determination of the nature of the field and itsalteration in response to different electrode distances, distancesbetween driving electrodes, wall thicknesses, and wall conductivities.The percentage of total current in the lumen of the vessel (% I) can beused as an index of both leakage and field homogeneity. Hence, thevarious geometric and electrical material properties can be varied toobtain the optimum design, i.e., minimizing the non-homogeneity of thefield. Furthermore, the experimental procedure was simulated byinjection of the two solutions of NaCl to verify the accuracy ofEquation [5]. Finally, the effect of the presence of electrodes and thecatheter in the lumen of vessel was assessed. The error termsrepresenting the changes in measured conductance due to the attractionof the field to the electrodes and the repulsion of the field from theresistive catheter body were quantified.

Poisson's equation was solved for the potential field, which takes intoaccount the magnitude of the applied current, the location of thecurrent driving and detection electrodes, and the conductivities andgeometrical shapes in the model including the vessel wall andsurrounding tissue. This analysis suggests that the following conditionsare optimal for the cylindrical model: (1) the placement of detection(voltage sensing) electrodes equidistant from the excitation (currentdriving) electrodes; (2) the distance between the excitation electrodesshould be much greater than the distance between the detectionelectrodes; and (3) the distance between the detection and excitationelectrodes is comparable to the vessel diameter, or the diameter of thevessel is small relative to the distance between the driving electrodes.If these conditions are satisfied, the equipotential contours moreclosely resemble straight lines perpendicular to the axis of thecatheter and the voltage drop measured at the wall will be nearlyidentical to that at the center. Since the curvature of theequipotential contours is inversely related to the homogeneity of theelectric field, it is possible to optimize the design to minimize thecurvature of the field lines. Consequently, in one approach, one or moreof conditions (1)-(3) described above are met to increase the accuracyof the cylindrical model.

Theoretically, it is impossible to ensure a completely homogeneous fieldgiven the current leakage through the lumen wall into the surroundingtissue. It was found that the iso-potential line is not constant as onemoves out radially along the vessel as stipulated by the cylindricalmodel. FIGS. 11A and 11B show the detected voltage for a catheter with aradius of 0.55 mm for two different NaCl solutions (0.5% and 1.5%,respectively). The origin corresponds to the center of the catheter. Thefirst vertical line 220 represents the inner part of the electrode whichis wrapped around the catheter, and the second vertical line 221 is theouter part of the electrode in contact with the solution (diameter ofelectrode is approximately 0.25 mm). The six different curves, top tobottom, correspond to six different vessels with radii of 3.1 mm, 2.7mm, 2.3 mm, 1.9 mm, 1.5 mm, and 0.55 mm, respectively. It can be seenthat a “hill” 220, 221 occurs at the detection electrodes, followed by afairly uniform plateau in the vessel lumen, followed by an exponentialdecay into the surrounding tissue. Since the potential difference ismeasured at the detection electrode 220, 221, the simulation generatesthe “hill” whose value corresponds to the equivalent potential in thevessel as used in Equation [5]. Thus, for each catheter size, thedimension of the vessel was varied such that Equation [5] was exactlysatisfied. Consequently, the optimum catheter size for a given vesseldiameter was obtained such that the distributive model satisfies thelumped equations (Equations [5] and [6]). In this way, a relationshipbetween vessel diameter and catheter diameter can be generated such thatthe error in the CSA determination is less than 5%. In one embodiment,different diameter catheters are prepackaged and labeled for optimal usein certain size vessel. For example, for vessel dimensions in the rangeof 4 mm to 5 mm, 5 mm to 7 mm, or 7 mm to 10 mm, analysis shows thatoptimum diameter catheters will be in the range of 0.9 mm to 1.4 mm, 1.4mm to 2 mm, or 2 mm to 4.6 mm, respectively. The clinician can selectthe appropriate diameter catheter based on the estimated vessel diameterof interest. This decision will be made prior to the procedure and willserve to minimize the error in the determination of lumen CSA.

Thus, a number of the embodiments disclosed herein accurately calculatelumen cross-sectional area by measuring conductance and correcting forvarious errors inherent in such measurements. However, at least some ofthe disclosed embodiments provide for the localization of body lumenjunctions and other intraluminal anatomical structures using relativeconductances and/or cross-sectional areas. Because only relativedifferences in conductance or cross-sectional area are necessary foraccurate localization, the calculation of absolute values for variouslocations within the body lumen may be skipped in most instances.

While various embodiments of devices, systems, and methods forlocalization of body lumen junctures have been described in considerabledetail herein, the embodiments are merely offered by way of non-limitingexamples of the invention described herein. Many variations andmodifications of the embodiments described herein will be apparent toone of ordinary skill in the art in light of the this disclosure. Itwill therefore be understood by those skilled in the art that variouschanges and modifications may be made, and equivalents may besubstituted for elements thereof, without departing from the scope ofthe invention. Indeed, this disclosure is not intended to be exhaustiveor to limit the scope of the invention. The scope of the invention is tobe defined by the appended claims, and by their equivalents.

Further, in describing representative embodiments, the disclosure mayhave presented a method and/or process as a particular sequence ofsteps. However, to the extent that the method or process does not relyon the particular order of steps set forth herein, the method or processshould not be limited to the particular sequence of steps described. Asone of ordinary skill in the art would appreciate, other sequences ofsteps may be possible. Therefore, the particular order of the stepsdisclosed herein should not be construed as limitations on the claims.In addition, the claims directed to a method and/or process should notbe limited to the performance of their steps in the order written, andone skilled in the art can readily appreciate that the sequences may bevaried and still remain within the spirit and scope of the presentinvention.

It is therefore intended that the invention will include, and thisdescription and the appended claims will encompass, all modificationsand changes apparent to those of ordinary skill in the art based on thisdisclosure.

The invention claimed is:
 1. A system, comprising: a display; a catheterdevice having a proximal end and a distal end, the distal end of thedevice for placement into a body lumen, the distal end including a pairof electrodes to collect relative conductance values, wherein eachelectrode of the pair of electrodes serves an excitation function and adetection function, and wherein a delay occurs between performance ofthe excitation function and performance of the detection function; and aprocessor coupled to the sensor and the display, the processorconfigured to construct a profile illustrating a first relativeconductance at a first location within the body lumen based on firstrelative conductance values of collected relative conductance values anda second relative conductance at a second location within the body lumenbased on second relative conductance values of the collected relativeconductance values, wherein the profile illustrates a junction of thebody lumen when a change in relative conductance between the firstlocation and the second location is detected by way of the electrodes,the first location being different from the second location.
 2. Thesystem of claim 1, wherein the body lumen comprises a lumen selectedfrom the group consisting of, at least a portion of: an atrium, apulmonary vein-atrial junction, a blood vessel, a biliary tract, or anesophagus.
 3. The system of claim 1, wherein the pair of electrodes areimmersed within a fluid within the body lumen and the fluid comprisesblood.
 4. The system of claim 1, wherein a proximal end of each of thepair of electrodes are communicatively coupled to the processor.
 5. Thesystem of claim 1, wherein the processor executes one or moreinstructions for analyzing the collected conductance values andconstructing the profile.
 6. A system, comprising: a display; a catheterdevice having a proximal end and a distal end, the distal end of thedevice for placement into a body lumen, the distal end including a pairof electrodes to collect first relative conductance values from a firstlocation within the body lumen and second relative conductance valuesfrom a second location within the body lumen, the first locationdifferent from the second location, wherein each electrode of the pairof electrodes serves an excitation function and a detection function,and wherein a delay occurs between performance of the excitationfunction and performance of the detection function; and a processorcoupled to the sensor and the display, the processor configured toconstruct a profile illustrating a first relative conductance based onthe first relative conductance values and a second relative conductancebased on the second relative conductance values, wherein the profileillustrates a junction of the body lumen when a change in relativeconductance between the first location and the second location isdetected through the electrodes.
 7. The system of claim 1, wherein thepair of electrodes are configured to collect the first relativeconductance values at a first time and the second relative conductancevalues at a second time.
 8. The system of claim 6, wherein the pair ofelectrodes are configured to collect the first relative conductancevalues at a first time and the second relative conductance values at asecond time.
 9. A system, comprising: a display; a catheter devicehaving a proximal end and a distal end, the distal end including a pairof electrodes configured to detect relative conductance while the deviceis advanced along a body lumen, wherein: each electrode of the pair ofelectrodes is configured to perform an excitation function and adetection function, and a delay occurs between performance of theexcitation function and performance of the detection function; and aprocessor coupled to the sensor and the display, the processorconfigured to construct a profile illustrating the relative conductanceas a function of location along the body lumen, the profile including atleast a first relative conductance at a first location along the bodylumen and a second relative conductance at a second location along thebody lumen that is different than the first location, the profileindicating a junction of the body lumen when a change in the relativeconductance is detected by the electrodes between the first location andthe second location.